Rotating night-shift work (hereafter referred to as shift work) has been associated with an increased risk of several cancers with evidence compelling enough to classify it as a class 2A, probable carcinogen by the International Agency for Research on Cancer. The main proposed mechanism for this association is that exposure to artificial light during night hours leads to disrupted levels of melatonin and an increased risk of carcinogenesis. Colorectal cancer is the third most common cancer in the United States. Unlike many cancers, colorectal cancer has a precursor lesion, adenoma, which can be detected and removed during routine screening endoscopy. Although the evidence for an association between night-shift work and colorectal cancer has been reported in one study, it is unknown at what stage night-shift work is acting on the natural history of the disease. Habitual duration of sleep has been shown to influence overall health, possibly via its relationship with melatonin and/or insulin levels. A meta-analysis reported that both short and long sleepers had an increased risk of mortality. The evidence for duration of sleep and the risk of specific cancers has been equivocal, and only one published study has evaluated the association between sleep duration and colorectal adenoma. We propose to determine whether shift work and habitual sleep duration have an impact on the development of colorectal adenoma by conducting a prospective study among participants in the Nurses' Health Study II (NHS II), a large prospective cohort of women. Specifically, we propose to evaluate the following hypotheses: 1) Longer duration of night shift-work is associated with an increased risk of colorectal adenoma, 2) Lower melatonin secretion (assessed by urinary melatonin [aMT6-s] levels) is associated with an increased risk of colorectal adenoma, and 3) Longer (and shorter) habitual duration of sleep are associated with a higher risk of colorectal adenoma. Our findings will lead to a better understanding of the effects of melatonin on carcinogenesis and will be the first study to specifically evaluate whether objectively measured melatonin levels are associated with colorectal adenoma. The results from this proposal will provide the critical groundwork for future, larger studies to disentangle the complex biological interactions between melatonin and colorectal adenoma, colorectal cancer and other cancers. Moreover, our findings can lead to targeted primary (diet, lifestyle) and secondary (screening) prevention guidelines for U.S workers who may be at higher risk of this important disease due to their occupation.